Current conceptions of sepsis-induced multiple organ dysfunction invoke a biphasic time course in which early overexpression of proinflammatory responses initiated by TNFa and members of the its superfamily including Fas (Apo-1, CD95) are followed by a secondary state of immunosuppression and susceptibility to infectious complications. TNFa- and Fas-mediated necrosis and apoptosis both result in cell death during sepsis. However, the balance between these two processes may critically determine the extent and progression of initial inflammation if the release of phlogistic constituents following necrotic cellular death is disproportionately enhanced. Apoptotic cell death may limit the degree of otherwise inevitable TNFa/Fas ligand (FasL)-mediated necrosis, even though apoptotic cell losses in the bone marrow, thymus, and lymph nodes may compromise host defense. Although important, the determinants of proinflammatory vs. apoptotic sequelae in response to increased production of TNFa and FasL, the specific cell surface receptors involved, and the exact signal transduction pathways are poorly understood at the whole animal level.